Imaging No Help in Endovascular Tx for Stroke

Action Points

A study looked at patients who were within 8 hours after the onset of large vessel, anterior circulation strokes and who underwent pretreatment CT or MRI of the brain and then were randomly assigned to undergo embolectomy or to receive standard care.

Note that a favorable penumbral pattern on neuroimaging did not identify patients who would benefit from endovascular therapy for acute ischemic stroke and further, embolectomy was not superior to standard care.

Overall, patients receiving embolectomy or standard stroke care had the same mean modified Rankin score (3.9) at 90 days, Chelsea S. Kidwell, MD, of Georgetown University Hospital in Washington, and colleagues reported here at the International Stroke Conference and simultaneously in the New England Journal of Medicine.

The SYNTHESIS and IMS-III trials reported here earlier also did not find that endovascular therapy in ischemic stroke was superior to standard therapy.

But Kidwell and colleagues also stratified patients according to whether imaging identified favorable penumbral patterns (substantial salvageable tissue and small infarct core) or unfavorable penumbral patterns (large core or small or absent penumbra).

"One possible explanation is that the penumbral pattern may identify patients who are likely to have a better outcome regardless of treatment because they have sufficient perfusion through collateral vessels to limit infarct size," commented Marc I. Chimowitz, MB, ChB, of the Medical University of South Carolina in Charleston, in an editorial that accompanied the NEJM publication.

"We think that this imaging approach is still very promising in future clinical trials," Kidwell told MedPage Today.

Infarct Blood Flow Studied

Perfusion imaging uses sophisticated software to color-code images according to areas of high (penumbral) and low (nonpenumbral) blood flow around the infarct.

Kidwell and colleagues hypothesized that a "favorable penumbral imaging pattern" might lend itself to endovascular therapy, particularly up to 8 hours after onset of symptoms.

Patients in the randomized, controlled MR RESCUE (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy) trial were enrolled at 22 centers in the U.S. within approximately 5.5 hours of their stroke onset. Their mean age was 65, and 48% were men.

Kidwell's data came from 118 patients -- 64 randomized to embolectomy and 54 to standard care.

Patients were further stratified by their imaging results:

Favorable penumbra -- embolectomy 34, standard care 34

Unfavorable penumbra -- embolectomy 30, standard care 20

The trial design called for patients randomized to embolectomy to be treated with any combination of FDA-cleared devices, which at the time included the Merci Retriever (since 2004) and the Penumbra System (since 2009). The trial was completed in 2011.

Kidwell later commented to MedPage Today that the emerging newer devices remove substantially more clot at a faster pace. Consequently, her data are not necessarily generalizable to newer devices.

Chimowitz agreed that more effective endovascular devices and lytic agents are needed to treat ischemic stroke. He offered optimism based on small studies for newer-generation devices and drugs that appear to be better than their first-generation cousins.

Early Recanalization Works Better

The design of MR RESCUE also allowed for intra-arterial rescue therapy with intravenous tissue plasminogen activator (tPA) within 6 hours after symptom onset. Eight patients needed to be rescued this way.

The thrombolytic tPA is the only such substance approved by the FDA for lysis of ischemic clots. The problem is that not all patients benefit from this strategy. So the search has continued for the right combination of devices, drugs, or techniques to be used intra-arterially or endoscopically.

Although intra-arterial treatment tends to open blocked arteries faster than IV tPA, the endovascular approach takes longer to set up, mainly because it must be performed in a cath lab. And as is the case with IV tPA that early treatment is associated with better outcomes, the same is true with endovascular therapy.

An analysis of IMS-III data by Pooja Khatri, MD, of the University of Cincinnati Academic Health Center, and colleagues showed that early endovascular recanalization was linearly correlated with better outcomes.

"The main message of this analysis is we have established that time from symptom onset to recanalization is important. This has not been shown before regarding endovascular therapy," Khatri told MedPage Today.

Imaging was important in MR RESCUE, and researchers set up two protocols for processing the perfusion scans. Investigators processed the images onsite in real time, but the images were also processed in a core laboratory.

Overall, 67% of patients in the endovascular treatment arm achieved successful recanalization as measured by the modified TICI (Thrombolysis In Cerebral Infarction) scores of 2a to 3.

Safety data showed an overall 21% rate of all-cause death, 4% rate of symptomatic hemorrhage, and 58% of asymptomatic hemorrhage. These results were consistent across the four groups in pairwise comparisons, Kidwell noted.

Different Brain Imaging Considered

However, the functional outcome results of MR RESCUE are not consistent with the conclusions of a substudy of the observational DEFUSE-2 study, which suggested that a slightly different brain imaging strategy could predict patients who benefited from embolectomy.

In this substudy, Hayley M. Wheeler, BS, from the Stanford Stroke Center in Stanford, Calif., and colleagues found that an early diffusion-weighted MR scan highly correlated with the final infarct size in patients who were recanalized.

This suggests that "permanent diffusion-weighted imaging reversal is minimal after endovascular reperfusion," researchers wrote in Stroke: Journal of the American Heart Association, where the study was simultaneously published to coincide with its presentation at the International Stroke Conference here.

Hayley and colleagues also found that early perfusion-weighted imaging was highly correlated with final infarct size in those who did not achieve reperfusion.

"Our hypothesis was that the baseline diffusion-weighted imaging represents the ischemic core and the follow-up perfusion-weighted imaging represents the tissue that was not salvaged by reperfusion; thus, the union of these two volumes should predict the final infarct," they concluded.

Imaging will very much remain a significant part of treating ischemic strokes intra-arterially, Kidwell and others noted. The key now is to refine imaging protocols and test them against the new devices and drugs that are coming onto the market, she said.

The MR RESCUE study was supported by the National Institute of Neurological Disorders and Stroke. Concentric Medical provided study catheters and devices from study start until August 2007; thereafter, costs for all study catheters and devices have been covered by study funds or third-party payers.

Kidwell reported relationships with relationships with Simcere and Embrella. Some co-authors reported relationships with industry, including Covidien, Medina, Grifols, Concentric Medical, MicroVention, Genentech, CoAxia, Paion, Forest, Lundbeck, Actelion, Xigen, Mitsubishi-Pharma, GE Healthcare, Philips Healthcare, Aldagen/Cytomedix, Penumbra, and Remedy Pharmaceuticals. It was also reported that the University of California has a patent on retrieval devices for stroke.

Funding for the DEFUSE 2 study was provided by the National Institute for Neurological Disorders and Stroke and the Stanford Medical Scholars Fellowship Program.

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.